More than half of the US adult population is overweight or obese,1 and the prevalence is particularly high among women.
Obesity increases the risk of several chronic diseases, including coronary
heart disease,2 type 2 diabetes,3 hypertension,4 stroke,5 and some cancers,
particularly colon cancer6 and postmenopausal
breast cancer.7 Intervention strategies to
combat this epidemic are needed. Physical activity may provide a low-risk
method of preventing weight gain and promoting maintenance of weight loss
in overweight and obese women.8 Unlike diet-induced
weight loss, exercise-induced weight loss increases cardiorespiratory fitness
levels.9

The Physical Activity for Total Health Study was a randomized, controlled,
year-long intervention trial designed to examine the effects of exercise vs
control on sex hormone concentrations (as biomarkers of breast cancer risk)
among sedentary, overweight, postmenopausal women.10 The
analyses described in this article examine the effects of this exercise intervention
on total and intra-abdominal body fat and evaluate the exercise effect among
subgroups specified by age, baseline adiposity, and adherence to the exercise
intervention.

Methods

Details of the aims and design of the study have been published previously.10,11 The study, conducted from 1997 to
2001, was a randomized controlled trial comparing the effect of a year-long
exercise vs control group on body fat and sex hormone concentrations measured
3 and 12 months after randomization. The intervention included a 3-month exercise
program intensively monitored by an exercise physiologist at a facility (University
of Washington, Seattle, and a commercial gym) followed by a 9-month program
primarily occurring at participants' homes. The study and protocol were approved
by the Fred Hutchinson Cancer Research Center Institutional Review Board.
Written informed consent was also obtained in accordance with the requirements
of the Fred Hutchinson Cancer Research Center Institutional Review Board.

Participants

We selected the study population to maximize the possible effects of
exercise on endogenous sex hormones and to avoid other factors known to affect
sex hormones. Participants were postmenopausal women from the greater Seattle
area who were aged 50 to 75 years, were sedentary at baseline (<60 min/wk
of moderate- and vigorous-intensity recreational activity and maximal oxygen
consumption <25.0 mL/kg per minute), had a body mass index (BMI; calculated
as weight in kilograms divided by the square of height in meters) of more
than 25.0 (or a BMI of 24.0-25.0 and body fat >33.0%), were not taking hormone
replacement therapy, had no clinical diagnosis of diabetes and had fasting
blood glucose levels of less than 140 mg/dL (7.8 mmol/L),12 and
were nonsmokers.

We recruited women through a combination of mass mailings and media
placements. Details on recruitment have been published elsewhere.11 After a telephone call to potential participants
to determine interest in the study, eligible women were scheduled for 3 baseline
clinic visits (a physical examination, a cardiorespiratory fitness assessment,
and dual-energy x-ray absorptiometry [DXA] and computed tomography [CT] scans).
After further determining eligibility and study interest, we randomly assigned
173 women to either the exercise intervention (n = 87) or the control group
(n = 86) (Figure 1). Randomization
was performed by random number generation and group assignment was placed
in a sealed envelope, which was opened by the study coordinator at the time
of randomization. Randomization was stratified by BMI (<27.5 vs ≥27.5)
to ensure equal numbers of heavier and lighter women in each study group.

Baseline and Follow-up Measures

We collected demographic and medical history information at baseline
and at 3- and 12-month visits. We measured total energy intake at baseline,
3 months, and 12 months via a 120-item self-administered food frequency questionnaire.13

We assessed current (past 3 months) physical activity at baseline, 3
months, and 12 months among exercisers and controls. In a self-administered
adaptation of the Minnesota Physical Activity Questionnaire,14 women
reported whether they did any of the 38 recreational or household activities
listed during the past 3 months. For the activities performed, the women recorded
the number of days per week and minutes per session.

We assessed maximal oxygen consumption at baseline and 12 months. Participants
completed a maximal-graded treadmill test, with heart rate and oxygen uptake
monitored by an automated metabolic cart (Medgraphics, St Paul, Minn). The
test began at 3.0 mph and 0% grade. The speed or grade (2% increments) of
the treadmill increased every 2 minutes (eg, stage 2: 3.5 mph, 0% grade; stage
3: 3.5 mph, 2% grade; stage 4: 3.5 mph, 4% grade) until the participant reached
volitional fatigue or experienced angina, lightheadedness, a drop in systolic
blood pressure, an excessive rise in systolic blood pressure to more than
250 mm Hg or in diastolic blood pressure to more than 120 mm Hg, or more than
4-mm down-sloping ST depression in any lead.15 No
treadmill tests in participants were terminated for reasons other than volitional
fatigue.

We measured baseline, 3-month, and 12-month weight and height to the
nearest 0.1 kg and 0.1 cm, respectively, by using a balance-beam scale and
stadiometer. Both measurements were taken in duplicate and averaged. Coefficients
of variation of replicate measures of weight and height, measured by the same
technician, were 0.05% and 0.2%, respectively. Waist and hip circumferences
were measured at baseline, 3 months, and 12 months to the nearest 0.1 cm using
an anthropometric fiberglass tape measure. Both measurements were taken in
duplicate using specified landmarks and then averaged. Coefficients of variation
of replicate readings of waist and hip circumferences, measured by the same
technician, were 0.3% and 0.2%, respectively.

We assessed total body fat and body fat percentage using a DXA whole-body
scanner (Hologic QDR 1500, Hologic Inc, Waltham, Mass). A whole-body scan
takes approximately 30 minutes to complete. With the participant lying on
the examination table in the supine position, a scan of the entire body was
performed. All DXA scans were performed by a technician blinded to the participants'
group randomization.

We measured intra-abdominal and subcutaneous fat with CT (General Electric
model CT 9800 scanner, Waukesha, Wis) at baseline and 12 months. One scan
was performed using a lateral-view radiograph of the skeleton (abdominal area)
to establish the position of the L4-L5 space within 1.0 mm. A second scan
was then performed at the L4-L5 space (at 125 kV and with a slice thickness
of 8 mm). One technician measured subcutaneous and intra-abdominal fat areas
using a software application (Image Analysis, Waukesha, Wis) that identifies
and measures each of the areas of interest by tracing lines around them and
computing the circumscribed areas. Coefficients of variation of replicate
measures of subcutaneous and intra-abdominal body fat, measured by the same
technician, were 1.2% and 1.5%, respectively.

Exercise Intervention

The exercise intervention consisted of at least 45 minutes of moderate-intensity
exercise 5 d/wk for 12 months. During months 1 through 3, participants were
required to attend 3 sessions per week at one of the study facilities and
to exercise 2 d/wk at home. For months 4 through 12, participants were required
to attend at least 1 session per week at the facility and to exercise the
remaining days on their own for a total of 5 d/wk (participants were allowed
to exercise additional days at the facility if they chose). The training program
began with a target of 40% of maximal heart rate for 16 minutes per session
and gradually increased to 60% to 75% of maximal heart rate for 45 minutes
per session by week 8, at which point it was maintained for the duration of
the study. Participants wore heart rate monitors (Polar Electro Inc, Woodbury,
NY) during their exercise sessions.

Facility sessions consisted of treadmill walking and stationary bicycling.
Strength training, consisting of 2 sets of 10 repetitions of leg extension,
leg curls, leg press, chest press, and seated dumbbell row, was recommended
but not required to decrease risk of injury and maintain joint stability.
A variety of home exercises were suggested and encouraged, including walking,
aerobics, and bicycling. Participants were encouraged to wear their heart
rate monitors when exercising at home.

Women randomly assigned to the control group attended weekly 45-minute
stretching sessions for 1 year and were asked not to change other exercise
habits during the study. Exercise and control participants were asked to maintain
their usual diet.

Measure of Exercise Adherence

The exercise intervention participants kept daily activity logs of all
sports or recreational activities they performed. They recorded type of exercise,
peak heart rate, rating of perceived exertion (scale, 6-20),16 and
duration of exercise. Each week, exercise trainers reviewed the logs for completeness
and clarity.

We used data from the daily activity logs as the primary measurement
of adherence. We included only activities that were sports or recreational
activities of at least 3 metabolic equivalents (METs) (based on the Compendium
of Physical Activities17), such as brisk walking
(a 3.8-MET level) and stationary bicycling (a 5.5-MET level). We defined good
adherence as meeting 80% of the exercise prescription (ie, 80% of 225 minutes
per week of moderate-intensity sports/recreational exercise).

Intervention Strategies

We used several techniques for promoting adherence, including individualized
attention in facility classes; group exercise behavior–change education
classes; weekly telephone calls to promote adherence; individual meetings
at baseline and every 3 months to outline goals and provide feedback on progress;
incentives; quarterly newsletters; and group activities such as hikes.

Statistical Analysis

We calculated duration (minutes per week of exercise) and change in
cardiorespiratory fitness level at 12 months. All analyses were based on assigned
treatment at the time of randomization, regardless of adherence or compliance
status (ie, intent-to-treat). A small number of 12-month body composition
data were not available. No change from the baseline values was assumed for
these missing values in the intent-to-treat analysis.

For both the exercise intervention and control groups, we computed the
mean change from baseline in body composition at 3 and 12 months after randomization.
Differences between intervention and control trends in body composition changes
from baseline through 3 and 12 months were assessed. To account for the longitudinal
nature of the data, we used a generalized estimating equation modification
of the linear regression model in making inferences.18

We also conducted stratified analyses to explore between-group differences
in body composition changes stratified by baseline age (<60, 60-69, or
≥70 years) and BMI (<27.6, 27.6-29.9, or ≥29.9). As a secondary analysis,
we compared the mean changes at 12 months across tertiles of measures of adherence.
All statistical tests were 2-sided. Statistical analyses were performed using
SAS software, version 8.2 (SAS Institute Inc, Cary, NC).

Results

Complete body weight, BMI, and circumference data were available for
all 173 participants at 3 months and for 168 women at 12 months (3 dropped
out and 2 refused 12-month measures). Complete DXA and CT data were available
for 167 women and 160 women at 12 months, respectively. Baseline demographic
and body composition data in the intervention and control groups were similar
(Table 1). Participants were a
mean age of 61 years and were highly educated. Less than a third worked full
time; 86% were non-Hispanic white, 4% were African American, and 6% were Asian
American.

Eighty-three percent of the 4524 expected activity logs were completed
(about 43 weeks of activity data per exerciser). A total of 24 320 activities
were recorded in the logs, reflecting 38 different activities (Table 2). Heart rate was available for 68% of the activities; mean
(SD) heart rate was 81% (9%) of maximal heart rate. The exercisers participated
in moderate-intensity sports/recreational activity for a mean (SD) of 3.5
(1.2) d/wk for 176 (91) min/wk. Six exercisers (8%) dropped out of the exercise
intervention (all after 3 months); however, 3 of the 6 returned for the 12-month
clinic visit and are used in the analyses. Among the control group, 6 participants
(7%) reported an increase of at least 225 min/wk of moderate-intensity sports/recreational
activity from baseline on the 12-month physical activity questionnaire.

Mean 3- and 12-month changes from baseline in body composition for both
groups are shown in Table 3. After
12 months, exercisers lost an average of 1.3 kg compared with a 0.1-kg weight
gain in controls (P = .01). The exercise group lost
an average of 8.5 g/cm2 of intra-abdominal body fat compared with
a slight gain (0.1 g/cm2) among the control
group (P = .045). Statistically significant between-group
differences in body weight (P = .05), BMI (P = .04), and hip circumference (P =
.01) occurred over time (P<.05 for trend), with
greater between-group differences observed at 12 months than at 3 months.

The mean change in body composition at 12 months among exercise and
control participants, stratified by age and BMI at baseline, is shown in Table 4. Between-group differences in the
changes in body weight and body fat at 12 months did not vary by age or BMI.

Changes in total body fat percentage, measured by DXA at 12 months and
stratified by tertiles of duration and changes in cardiorespiratory fitness
level, are shown in Figure 2. Women
who exercised for more than 195 min/wk (highly active) lost 4.2% of total
body fat compared with losses of 2.4% among intermediate-activity exercisers
(136-195 min/wk), 0.6% among low-activity exercisers (≤135 min/wk), and
0.4% among the control group between baseline and 12 months. A similar trend
of greater body-fat loss with increasing cardiorespiratory fitness level was
also observed.

The percentage change in intra-abdominal fat, measured by CT at 12 months
and stratified by duration and change in cardiorespiratory fitness level,
is shown in Figure 3. Women who
exercised for more than 195 min/wk (highly active) lost 6.9% of intra-abdominal
body fat compared with a loss of 5.9% among intermediate-activity exercisers
(136-195 min/wk), a loss of 3.4% among low-activity exercisers (≤135 min/wk),
and a gain of 0.1% among the control group between baseline and 12 months.
A similar trend of greater intra-abdominal body fat loss with increasing cardiorespiratory
fitness level was also observed. No injuries were reported as a result of
the exercise intervention.

Comment

This year-long moderate-intensity exercise program among overweight,
postmenopausal, previously sedentary women led to significant decreases in
body weight, total body fat, and intra-abdominal and subcutaneous abdominal
fat. Our finding of statistically significant between-group differences in
body weight changes over time indicates that long-term adherence to a facility-
and home-based exercise program is possible and results in prolonged and increasing
benefits.

While the body weight lost at 12 months among the exercisers was modest,
the amount of intra-abdominal fat lost was considerable (8.5 g/cm2)
and was dose-dependent. Only 2 randomized trials have been conducted previously
that examined the effect of exercise on intra-abdominal body fat, used imaging
techniques (eg, CT), and studied women.19,20 One
trial randomized 4 women with type 2 diabetes into an 8-week exercise intervention,19 and the other trial randomized 8 women into a 4-month
exercise intervention.20 Because of the small
sample sizes, the results were inconclusive.

Whether the effect of a diet-plus-exercise intervention would result
in greater loss of intra-abdominal fat among women is unknown. More studies
using imaging techniques such as CT to examine the effect of diet and/or exercise
on intra-abdominal fat are needed.

Intra-abdominal obesity is associated with insulin resistance, insulinlike
growth factors, type 2 diabetes, hypertension, dyslipidemia, and cardiovascular
disease.21-25 Exercise
may counteract the aberrant metabolic profile associated with intra-abdominal
obesity, both directly and as a consequence of body-fat loss. Numerous adaptive
responses take place with exercise training, including development of a more
efficient system for transfer of oxygen to muscle. With this more efficient
system, muscles can increase their use of lipid stores rather than relying
primarily on carbohydrate reserves.26 In addition,
exercise helps counteract the weight regain often observed after diet-induced
weight loss.27

According to meta-analyses conducted by Dattilo and Kris-Etherton28 and MacMahon et al,29 a
weight loss of 1 kg decreases serum cholesterol by 1% or 2.3 mg/dL (0.06 mmol/L),
triglycerides by 1.9% or 1.5 mg/dL (0.02 mmol/L), and fasting plasma glucose
by 3.6 mg/dL (0.2 mmol/L). Thus, a 5-kg weight loss would decrease average
fasting plasma glucose values by 18 mg/dL (1.0 mmol/L). This improvement is
in the range provided by many of the oral hypoglycemic agents that are currently
used, although the benefits of these medications usually decrease with time.
Furthermore, the Diabetes Prevention Program Research Group30 recently
showed that a weight loss goal of 7% and at least 150 min/wk of physical activity
significantly reduced incidence of type 2 diabetes by 58% in overweight adults.
Thus, consistent with the recommendation of the National Heart, Lung, and
Blood Institute and the American College of Sports Medicine, an initial weight-loss
goal should be to decrease body weight by 5% to 10% and to sustain this loss
over the long term.31

A limitation of our study was that the participants did not record the
duration for which they exercised at peak heart rate. Thus, we were unable
to accurately determine energy expenditure. However, when we used the peak
heart rate to examine the effect of energy expenditure per week on body fat,
trends and effect sizes similar to duration of exercise were observed. Another
limitation was that exercise performed at home was self-reported in the daily
activity log compared with exercise performed at the facility, which was both
self-reported and observed by the exercise trainer. Nonetheless, moderate-intensity
exercise appears to be an effective tool among those who are prepared to make
the necessary changes.

A major strength of our study was the excellent adherence to the exercise
program and the low dropout rate. We collected daily activity logs from participants
for each week of the study. Participants recorded data for each exercise session
on type of activity, duration, and peak heart rate (when available). These
data allowed us to determine dose-response associations between exercise and
body composition. Our results show a statistically significantly greater weight
and fat loss with exercise among women with stronger adherence to the exercise
intervention. Other strengths of the present study are the large sample size
(N = 173) compared with other randomized controlled trials on this topic (<25
participants) and the long study duration (1 year vs <6 months).

In conclusion, this randomized controlled trial of a moderate-intensity
exercise intervention produced significant between-group differences in baseline
to 12-month changes in body weight, total body fat, and intra-abdominal and
subcutaneous abdominal body fat. Previously sedentary postmenopausal women
who exercised for approximately 200 min/wk lost 4.2% of total body fat and
6.9% of intra-abdominal fat while maintaining their energy intake. This amount
of exercise is similar to current national recommendations (ie, 30 minutes
of moderate-intensity activity on most days of the week).32 Furthermore,
84% of the exercisers in this study improved their cardiorespiratory fitness.
High levels of cardiorespiratory fitness reduce the rate of cardiovascular
morbidity and mortality, independent of obesity.33 Statistically
significant between-group differences in body weight and BMI changes occurred
over time, even though the structured, intensely monitored aspect of the exercise
intervention lessened over time. Overweight women should be encouraged to
participate in moderate-intensity exercise as a method for obesity reduction
and chronic disease prevention. Our findings support the important role of
exercise in reducing body fat, especially intra-abdominal fat.